Phenylalanine enamide derivatives

Details Phenylalanine enamide derivatives Phenylalanine enamide derivatives

2005-03-29

2005-03-29

Stockton, Laura L. (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C514S252120, C514S278000, C544S070000, C544S230000, C546S015000

Reexamination Certificate

active

06872719

ABSTRACT:
Phenylalanine enamide derivatives of formula (1) are described:wherein R1is a —CH3, —(CH2)3CH3, —CH2CH2OH, —CH2CH2OCH3, —CH2CH2OCH2CH2OH, —CH2CH2OCH2CH2OCH3,group;and the salts, solvates and N-oxides thereof.Compounds according to the invention are potent and selective inhibitors of α4 integrins. The compounds are of use in modulating cell adhesion and in particular are of use in the prophylaxis and treatment of diseases or disorders including inflammation in which the extravasation of leukocytes plays a role and the invention extends to such a use and to the use of the compounds for the manufacture of a medicament for treating such diseases or disorders.

REFERENCES:
patent: WO 02068393 (2002-09-01), None
Abraham, W.M. et al., “α4-Integrins Mediate Antigen-Induced Late Bronchial Responses and Prolonged Airway Hyperresponsiveness in Sheep,”J. Clin. Invest., 1994, 93, 776-787.
Berlin, C. et al., “α4β7 Integrin Mediates Lymphocyte Binding to the Mucosal Vascular Addressin MAdCAM-1,”Cell, 1993, 74, 185-195.
Binns, R.M. et al., “The Role of E-Selectin in Lymphocyte and Polymorphonuclear Cell Recruitment into Cutaneous Delayed Hypersensitivity Reactions in Sensitized Pigs,”J. Immunol., 1996, 157, 4094-409.
Tiskin, M.J., et al., “Structural requirements for mucosal vascular addressin binding to its lymphocyte receptor α4β7,”J. Immunol., 1996, 156, 719-726.
Brooks, Peter C., et al., “Antiintegrin αvβ3 blocks human breast cancer growth and angiogenesis in human skin,”J. Clin. Invest., 1995, 96, 1815-1822.
Cardarelli, P.M. et al., “Cyclic RGD Peptide Inhibits α4β7 Interaction with Connecting Segment 1 and Vascular Cell Adhesion Molecule,”J. Biol. Chem., 1994, 269(28), 18668-18673.
Erle, D.J., et al., “Expression and function of the MadCAM-1 receptor, integrin α4β7, on human leukocytes,”J. Immunol., 1994, 153, 517-528.
Ferguson, T.A. et al., “Two integrin-binding peptides abrogate T cell-mediated immune responses in vivo,”Proc. Natl. Acad. Sci. USA, 1991, 88, 8072-8076.
Hammes, H., et al., “Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization,”Nature Medicine, 1996, 2, 529-533.
Hesterberg, P.E., et al., “Rapid resolution of chronic colitis in the cotton-top tamarin with an antibody to a gut-homing integrin α4β7,”Gastroenterol, 1996, 111, 1373-1380.
Hodivala-Dilke, K.M., “β3-integrin-deficient mice are a model for glanzmann thrombasthenia showing placental defects and reduced survival,”J. Clin. Invest., 1999, 103(2), 229-238.
Holzmann, B., et al., “Peyer's patch-specific lymphocyte homing receptors consist of a VLA-4-like α chain associated with either of two integrin β chains, one of which is novel,”EMBO J., 1989, 8(6), 1735-1741.
Humphries, M.J. et al., “Mechanisms of VCAM-1 and fibronectin binding to integrin α4β1: implications for integrin function and rational drug design,”Ciba Foundation Symposium, 1995, 189, 177-194.
Issekutz, T.B., “Inhibition of Lymphocyte Endothelial Adhesion and In Vivo Lymphocyte Migration to Cutaneous Inflammation by TA-3, a New Monoclonal Antibody to Rat LFA-1,”J. Immunol., 1992, 149(10), 3394-3402.
Li, Z. et al., “Effect of an anti-Mo1 MAb on ozone-induced airway inflammation and airway hyperresponsiveness in dogs,”Am. J. Physiol., 1992, 263(6 Pt 1), L723-726.
Marlin, S.D. et al., “LFA-1 Immunodeficiency Disease,”J. Exp. Med., 1986, 164, 855-867.
Mitjans, F., et al., “An anti-αv-integrin antibody that blocks integrin function inhibits the development of a human melanoma in nude mice,”J. Cell Science, 1995, 108, 2825-2838.
Newham, P., et al., “Integrin adhesion receptors: structure, function and implications for biomedicine,”Molecular Medicine Today, 1996, 304-313.
Osborne, L., “Leukoctye Adhesion to Endothelium in Inflammation,”Cell, 1990, 62, 3-6.
Podolsky, D.K. et al., “Attenuation of Colitis in the Cotton-top Tamarin by Anti-α4 integrin Monoclonal Antibody,”J. Clin. Invest., 1993, 92, 372-380.
Shroff, H.N., et al., “Small peptide inhibitors of α4β7mediated MadCAM-1 adhesion to lymphocytes,”Biorg. Med. Chem. Letts., 1996, 6(21), 2495-2500.
Sonnenberg, A., “Integrins and their ligands,”Curr. Topics Microbiol. Immunol., 1993, 184, 7-35.
Springer, T.A., “Adhesion receptors of the immune system,”Nature, 1990, 346, 425-434.
Springer, T.A., “Traffic Signals for Lymphocyte Recirculation and Leukocyte Emigration: The Multistep Paradigm,”Cell, 1994, 76, 301-314.
Srivatsa, S.S., et al., “Selective αvβ3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin αvβ3 and osteopontin expression during neointima formation,”Cariovascular Research, 1997, 36, 408-428.
Vanderslice, P. et al., “A Cyclic Hexapeptide is a Potent Antagonist of α4 Integrins,”J. Immunol., 1997, 158, 1710-1718.
Wasserman, H.H., et al., “Cyclobutenone derivatives from ethoxyacety;ene,”J. Org. Chem., 1973, 38(8), 1451-1455.
Yang, X., “A predominant role of integrin α4 in the spontaneous development of autoimmune diabetes in nonobese diabetic mice,”Proc. Natl. Acad. Sci. USA, 1994, 91, 12604-12608.
Yednock, T.A., “Prevention of experimental autoimmune encephalomyelitis by antibodies against α4β1 integrin,”Nature, 1992, 356, 63-66.

Affiliated with

Also associated with

Rating

Phenylalanine enamide derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Phenylalanine enamide derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Phenylalanine enamide derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3418113